Determinants of cyclophilin A-dependent TRIM5[alpha] restriction against HIV-1

@article{citeulike:3194339, abstract = {TRIM5[alpha] is a host protein that can bind to incoming retroviral capsid (CA) and inhibit retroviruses in a species-specific manner. The CA protein of HIV-1 also interacts with high affinity to the host protein cyclophilin A (CypA). This binding has been shown to positively affect some early stage of the viral life cycle in human cells. However, the CypA/CA interaction also renders HIV-1 more susceptible to rhesus TRIM5[alpha] (rhTRIM5[alpha]) restriction. We find that the ability of old world monkey TRIM5[alpha] genes to restrict HIV-1 in a CypA-dependent manner is widespread. On the other hand, we find that simian immunodeficiency viruses from tantalus monkeys (SIVagmTAN), is unlike HIV-1 in that CypA does not enhance the rhTRIM5[alpha] restriction against the virus even though the CA of this virus, like HIV-1, does bind CypA. Mapping of the determinants for this phenotype by swapping regions on CA between SIVagmTAN and HIV-1 showed that when SIVagmTAN contains loops between helices 4/5 (4-5 loop) and 6/7 (6-7 loop) from HIV-1 CA, it becomes susceptible to the CypA-enhanced rhTRIM5[alpha] restriction. Surprisingly, when SIVagmTAN contains either loop from HIV-1 CA, it gains sensitivity to TRIM5[alpha] from species which originally have no effect on the wild-type virus. Moreover, we find that CypA/CA interaction occurs early after viral entry but the CypA-enhanced restriction mostly acts on the stage after reverse transcription.}, author = {Lin, Tsai-Yu and Emerman, Michael }, citeulike-article-id = {3194339}, doi = {http://dx.doi.org/10.1016/j.virol.2008.06.037}, journal = {Virology}, keywords = {hiv, innate}, month = {September}, number = {2}, pages = {335--341}, posted-at = {2008-09-04 16:47:30}, priority = {2}, title = {Determinants of cyclophilin A-dependent TRIM5[alpha] restriction against HIV-1}, url = {http://dx.doi.org/10.1016/j.virol.2008.06.037}, volume = {379}, year = {2008} }

TY - JOUR ID - citeulike:3194339 L3 - citeulike-article-id:3194339 N2 - TRIM5[alpha] is a host protein that can bind to incoming retroviral capsid (CA) and inhibit retroviruses in a species-specific manner. The CA protein of HIV-1 also interacts with high affinity to the host protein cyclophilin A (CypA). This binding has been shown to positively affect some early stage of the viral life cycle in human cells. However, the CypA/CA interaction also renders HIV-1 more susceptible to rhesus TRIM5[alpha] (rhTRIM5[alpha]) restriction. We find that the ability of old world monkey TRIM5[alpha] genes to restrict HIV-1 in a CypA-dependent manner is widespread. On the other hand, we find that simian immunodeficiency viruses from tantalus monkeys (SIVagmTAN), is unlike HIV-1 in that CypA does not enhance the rhTRIM5[alpha] restriction against the virus even though the CA of this virus, like HIV-1, does bind CypA. Mapping of the determinants for this phenotype by swapping regions on CA between SIVagmTAN and HIV-1 showed that when SIVagmTAN contains loops between helices 4/5 (4-5 loop) and 6/7 (6-7 loop) from HIV-1 CA, it becomes susceptible to the CypA-enhanced rhTRIM5[alpha] restriction. Surprisingly, when SIVagmTAN contains either loop from HIV-1 CA, it gains sensitivity to TRIM5[alpha] from species which originally have no effect on the wild-type virus. Moreover, we find that CypA/CA interaction occurs early after viral entry but the CypA-enhanced restriction mostly acts on the stage after reverse transcription. IS - 2 JF - Virology EP - 341 TI - Determinants of cyclophilin A-dependent TRIM5[alpha] restriction against HIV-1 VL - 379 SP - 335 KW - hiv KW - innate AU - Lin, Tsai-Yu AU - Emerman, Michael PY - 2008/09/30/ UR - http://dx.doi.org/10.1016/j.virol.2008.06.037 ER -